A historical review of cellular calcium handling,with emphasis on mitochondria

Calcium ions are of central importance in cellular physiology, as they carry the signal activating cells to perform their programmed function. Ca²⁺ is particularly suitable for this role because of its chemical properties and because its free concentration gradient between the extra cellular and the cytosolic concentrations is very high, about four orders of magnitude. The cytosolic concentration of Ca²⁺ is regulated by binding and chelation by various substances and by transport across plasma and intracellular membranes. Various channels, transport ATPases, uniporters, and antiporters in the plasma mem brane, endoplasmic and sarcoplasmic reticulum, and mitochondria are responsible for the transport of Ca²⁺ .The regulation of these transport systems is the subject of an increasing number of studies. In this short review, we focus on the mitochondrial transporters, i.e. the calcium uniporter used for Ca²⁺ uptake, and the antiporters used for the efflux, i.e. the Ca²⁺/Na⁺ antiporter in mitochondria and the plasma membrane of excitable cells,and the Ca²⁺/nH⁺ antiporter in liver and some other mitochondrial types. Mitochondria are of special interest in that Ca²⁺ stimulates respiration and oxidative phosphorylation to meet the energy needs of activated cells. The studies on Ca²⁺ and mitochondria began in the fifties, but interest in mito chondrial Ca²⁺ handling faded in the late seventies since it had become apparent that mitochondria in resting cells contain very low Ca²⁺. Interest increased again in the nineties also because it was discovered that mitochondria and Ca²⁺ had a central role in apoptosis and necrosis. This is of special interest in calcium overload and oxidative stress conditions, when the opening of the mitochondrial permeability transition pore is stimulated.Translated from Biokhimiya,Vol. 70, No. 2, 2005, pp. 231–239.Original Russian Text Copyright © 2005 by Saris, Carafoli.This revised version was published online in April 2005 with corrections to the post codes.